通过分子对接和分子动力学模拟等理论方法研究(E) -2 -(乙酰胺亚甲基)琥珀酸(E - 2AMS)水解酶与其水解底物E- 2AMS的结合方式.MM_PBSA结合自由能计算结果和动力学轨迹的统计分析都表明,在E -2AMS与水解酶形成的复合结构中,底物酰胺键采取反式构型在能量上更有利.在这种结合方式中,水解酶活性位点处的关键残基Arg146、Arg167、Tyr168、Arg179和Tyr259与E- 2AMS之间形成7条氢键,在催化反应中起到稳定底物的作用；而残基Ile41和Leu107的主链氨基形成“氧负离子洞”,能够抵消催化过程中酰胺氧原子上积累的负电荷,有利于反应的顺利进行.%Molecular docking, molecular dynamics ( MD) simulation method were used to investigate the binding mode of (E) -2 - (Acetamidomethylene)succinate (E -2AMS) hydrolase to its substrate. The results from MM_ PBSA binding free energy calculation and the statistical analysis of the MD trajectories all show that the trans - amide configuration of E-2AMS is energetically favourable in the complex structure. In the binding mode, the key residues in the active site of hydrolase, Argl46, Argl67, Tyrl68,Argl79 and Tyr259 form seven H -bonds with E - 2AMS, which play an important role of stabilizing the substrate in the catalysis reaction. The main - chain amides of Ile41 and Leu 107 form an oxyanion hole and offset the negative charge that builds up during catalysis, which is helpful for the catalysis process.
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